title: The protective effect of low-dose methotrexate on ischemia-reperfusion injury of the rabbit spinal cord.
abstract: Methotrexate was developed as a cytostatic agent, but at low doses, it has shown potent anti-inflammatory activity. Previous studies have demonstrated that the anti-inflammatory effects of methotrexate are primarily mediated by the release of adenosine. In this study, we hypothesized that low-dose methotrexate has protective effects in spinal cord ischemia-reperfusion injury. Rabbits were randomized into the following four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (methotrexate). In the control group only a laparotomy was performed. In all the other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Neurological evaluation was performed with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, as were the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural evaluations were also performed. After ischemia-reperfusion injury, increases were found in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both serum and tissue catalase levels were decreased. After the administration of a low-dose of methotrexate, decreases were observed in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both the serum and tissue catalase levels were increased. Furthermore, low-dose methotrexate treatment showed improved results concerning the histopathological scores, the ultrastructural score and the Tarlov scores. Our results revealed that low-dose methotrexate exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.
authors.affiliation: Ministry of Health, Diskapi Yildirim Beyazit Education and Research Hospital, Department of Neurosurgery, Ankara, Turkey.
authors.forename: Hayri
authors.initials: H
authors.lastname: Kertmen
authors.forename: Bora
authors.initials: B
authors.lastname: Gürer
authors.forename: Erdal Reşit
authors.initials: ER
authors.lastname: Yılmaz
authors.forename: Ahmet Metin
authors.initials: AM
authors.lastname: Sanlı
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sorar
authors.forename: Ata Türker
authors.initials: AT
authors.lastname: Arıkök
authors.forename: Mustafa Fevzi
authors.initials: MF
authors.lastname: Sargon
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Kanat
authors.forename: Berrin Imge
authors.initials: BI
authors.lastname: Ergüder
authors.forename: Zeki
authors.initials: Z
authors.lastname: Sekerci
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014969:Xanthine Oxidase / Q000097:blood
chemical_list: D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D014969:Xanthine Oxidase; D053148:Caspase 3; D008775:Methylprednisolone; D008727:Methotrexate
keywords: Adenosine; Ischemia–reperfusion; Methotrexate; Methylprednisolone; Neuroprotection; Spinal cord